血清抗甲状腺球蛋白抗体和抗甲状腺过氧化物酶抗体检测在甲状腺疾病诊断及甲亢预后判断中的价值

采用放免法检测甲状豚疾病患者抗甲状腺球蛋白抗体（ＴＧＡｂ）和抗甲状腺过氧化物酶抗体（ＴＰＯＡｂ）、并对部分Ｇｒａｖｅｓ病患者停药后随诊一年的结果进行分析。结果显示：（１）自身免疫性甲状腺疾病患者ＴＧＡｂ和ＴＰＯＡｂ活性及阳性率明显高于非ＡＩＴＤ，尤以桥本甲状腺炎为然。（２）ＧＤ治疗前及停药时ＴＧＡｂ和ＴＰＯＡｂ均阴性者与均阳性者停药一年内的复发率分别为０．５８３和０．２３１。（３）ＴＧＡｂ和ＴＰＯＡｂ均阴性，而停药时甲状腺刺激抗体（ＴＳＡｂ）阳性者，停药时ＧＤ复发的机率最大（０．９０９），提示ＴＧＡｂ和ＴＰＯＡｂ检测在ＡＩＴＤ诊断，鉴别诊断以及ＧＤ预后判断中具有重要的临床意义。     

血清抗甲状腺球蛋白抗体和抗甲状腺过氧化物酶抗体检测在？…

采用放免法检测甲状腺疾病患者抗甲状腺球蛋白抗体（ＨＴＧＡｂ）和抗甲状腺过氧化物酶抗体（ＴＰＯＡｂ），并对部分Ｇｒａｖｅｓ病患者焦药后随诊一年的结果进行分析。结果显示：（１）自身免疫性甲状腺疾病患者ＴＧＡｂ和ＴＰＯＡｂ活性及阳性率及明显高于ＡＩＴＤ，尤以桥本甲状腺炎为然。（２）ＧＤ治疗前及停药时ＴＧＡｂＴ和ＴＧＡｂ和ＴＰＯＡｂ均阴性者与均阳性者停药一年内的复发率分别为０．５８３和０．２３１。（３）Ｔ     

Graves病患者治疗前、后血清甲状腺刺激抗体和TSH结合抑制免疫球蛋白活性的观察

本文研究了Ｇｒａｖｅｓ病（ＧＤ）患者在抗甲状腺药物（ＡＴＤ）治疗前、后血清甲状腺刺激抗体（ＴＳＡｂ）和ＴＳＨ结合抑制免疫球蛋白（ＴＢＩＩ）的变化，发现治疗前ＴＳＡｂ和ＴＢＩＩ的检出率分别为９１．７％和７９．２％，治疗后两抗体的活性及阳性率均显著下降，表明抗甲状腺药可改善ＧＤ患者的免疫异常。ＴＳＡｂ和ＴＢＩＩ活性不相关，提示ＴＳＨ受体抗体（ＴＲＡｂ）具有异质性。ＴＳＡｂ和ＴＢＩＩ活性与血清甲状腺激素水平无相关关系，说明体外测定的ＴＳＡｂ或／和ＴＢＩＩ活性并不能完全反映甲亢的严重程度。     

Graves病患者治疗前,后血清甲状腺激素抗体和TSH结合抑制免疫？…

本文研究了Ｇｒａｖｅｓ病（ＧＤ）患者在抗甲状腺药物（ＡＴＤ）治疗前、后血清甲状腺刺激抗体（ＴＳＡｂ）和ＴＳＨ结合抑制免疫球蛋白（ＴＢＩＩ）的变化，发现治疗前ＴＳＡｂ和ＴＢＩＩ的检出率分别为９１．７％和７９．２％，治疗后两抗体的活性及阳笥率均显著下降，表明抗甲状腺药可改善ＧＤ患者的免疫异常。ＴＳＡｂ和ＴＢＩＩ活性不相关，提示ＴＳＨ受体抗体（ＴＲＡｂ）具有异质性。ＴＳＡｂ和ＴＢＩＩ活性与血清甲状腺激素     

冷冻保存人甲状腺细胞的活力,功能和临床应用

本文研究冷冻保存不同时间甲状腺细胞的活力、功能及其在甲状腺刺激抗体（ＴＳＡｂ）检测中的应用。结果表明：冻存３、６和１２个月的正常或甲亢甲状腺细胞具有良好的活力，各冷冻时相的细胞对ＴＳＨ刺激生成ｃＡＭＰ的反应性无明显差异，且与未冷冻细胞的反应性相似。以冻存甲亢甲状腺细胞测定血清ＴＳＡｂ．在Ｇｒａｖｅｓ病（ＧＤ）未治组的检出率为０．９１３，而甲状腺腺瘤（甲瘤）组与对照组ＴＳＡｂ均为阴性。这提示冻存一年内的人甲状腺细胞仍保持较好的活性与功能，可以作为甲状腺功能和甲状腺疾病基础与临床研究的材料。     

自身抗体在甲状腺疾病诊断中的意义

自身抗体在甲状腺疾病诊断中的意义方先麟，胡宪蕴，安志远我们用ＲＩＡ和ＥＬＩＳＡ观察了８２例甲状腺疾病患者诊断及治疗前后血清Ｔ３、Ｔ４、ＴＳＨ、ＦＴ３、ＦＴ４、ＴＧＡｂ、ＴＭＡｂ及ＴＲＡｂ的浓度变化。甲状腺疾病患者８２例，女６５例，男１７例，年龄１４～...     

白细胞介素6在Graves病的发病及骨代谢中的作用

采用白细胞介素 ６依赖性细胞株ＭＨ６０· ＢＳＦ增殖反应ＭＴＴ法，测定了 ５３例 Ｇｒａｖｅｓ病（ＧＤ）患者外周血单个核细胞（ＰＢＭＣ）培养上清中ＩＬ－６水平。结果未治疗组、治疗未缓解 组 ＩＬ－６水平高于缓解组和对照组（Ｐ＜ ０． ０１），后两者间无差异（Ｐ＞ ０． ０５），ＩＬ－６与血清游离三 碘甲状腺原氨酸（ＦＴ３）、游离甲状腺素（ＦＴ４）、甲状腺微粒体抗体（ＴｍＡｂ）、甲状腺球蛋白抗体 （ＴｇＡｂ）、骨钙素（ＢＧＰ）呈正相关，与桡、尺骨密度均值（ＢＭＤ）呈负相关。提示ＩＬ－６在ＯＰ发病与骨 代谢中起作用。ＩＬ－６可作为ＧＤ患者治疗效果的判定和预后以及预防骨质疏松症（ＯＰ）发生的重要 指标。     

灵敏的甲状腺微粒体抗体酶联免疫吸附分析的建立

甲状腺微粒体抗体（ＴＭＡｂ）或称甲状腺过氧化物酶抗体（ＴＰＯ－Ａｂ）已广泛用于人类甲状腺自身免疫性疾病的诊断，但粗提的人甲状腺微粒体制备物含有残留的甲状腺球蛋白（ＴＧ）和其它膜抗原，影响方法的灵敏度，我们采用亲和层析的方法，得到纯度较高的ＴＭ抗原，建立了灵敏的ＴＭＡｂ－ＥＬＩＳＡ。该方法的批内变异系数为３．２±０．０１％（ｎ＝８０），批间变异系数为８．３±０．０２％（ｎ＝８）；临床甲亢病人的阳性率为８０．０％（ｎ＝４６），与国内同类放免试剂盒相比，对Ｇｒａｖｅｓ病的阳性检出率提高２０％（ｎ＝２０），桥本氏甲状腺炎的阳性检出率提高１１．７％（ｎ＝２６）。     

人甲状腺细胞的培养和功能研究及其应用

本文探讨获得正常和甲亢甲状腺细胞的方法及其培养条件，研究其对ＴＳＨ和甲状腺刺激抗体（ＴＳＡｂ）的反应性，分析两种甲状腺细胞在甲状腺特异性抗体测定中的临床价值。结果表明：１．正常和甲亢两种甲状腺组织经胰酶和胶原酶消化６０～９０分钟，即可获得大量活力良好的人甲状腺细胞；２．甲状腺细胞在以Ｅａｇｌｅ营养液为基础的培养条件下，随每孔细胞数的增多，对ＴＳＨ和ＴＳＡｂ刺激生成ｃＡＭＰ的量亦增加，并且在０～９６小时的培养时间里，甲状腺细胞ｃＡＭＰ的释放值递增；３．以正常或甲亢甲状腺细胞作为靶细胞，来检测病人血清ＴＳＡｂ和甲状腺刺激阻断抗体（ＴＳＢＡｂ），均具有较好的灵敏度和特异性。     

雷公藤抑制致敏小鼠CD4^＋T细胞核因子GATA3,NFAT的活性

目的 探讨致敏小鼠ＣＤ４＾＋Ｔ淋巴细胞核转录因子ＧＡＴＡ３、ＮＦＡＴ活性的变化及雷公藤内酯醇（ＴＰ）的作用。方法 采用卵蛋白（ＯＶＡ）致敏的方法建立模型；运用ｐａｎｎｉｎｇ法分离ＣＤ４＾＋Ｔ淋巴细胞；通过凝胶电泳迁移率实验（ＥＭＳＡ）对ＣＤ４＾＋Ｔ淋巴细胞核因子ＧＡＴＡ３、ＮＦＡＴ的ＤＮＡ结合活性及ＴＰ的作用进行检测，同时就ＴＰ的作用与地塞米松（ＤＭ）相比较。结果 正常小鼠ＣＤ４＾＋Ｔ淋巴细胞核因     

甲状腺自身抗体在自身免疫性甲状腺疾病诊断中的临床应用

目的 探讨患者血清甲状腺自身抗体——促甲状腺激素受体抗体(TRAb)、甲状腺过氧化物抗体(TPOAb)、甲状腺球蛋白抗体(TGAb)浓度的变化,在自身免疫性甲状腺疾病(AITD)中桥本甲状腺炎(hashimoto,HT)和毒性弥漫性甲状腺肿(Graves' disease,GD)的诊断意义.方法 选取2015年2月至8月我院收治200例患者,其中桥本甲状腺炎100例,Graves病100例,以及50例健康志愿者作为对照组.采用电化学发光法(ECLIA)检测TRAb,用放射免疫法(RIA)检测TPOAb和TGAb,并对比上述指标的检测结果.结果 自身免疫性甲状腺疾病(AITD)显著高于健康对照组,Graves病患者TRAb水平显著高于桥本甲状腺炎患者,而且桥本甲状腺炎患者TPOAb、TGAb水平显著高于Graves病患者,均有显著差异(P＜0.05).结论 TPOAb、TGAb在桥本甲状腺病诊断中起重要作用.而TRAb对于Graves病有较高的灵敏度和特异性,可以作为诊断Graves病的特异性指标.     

甲状腺球蛋白抗体和甲状腺过氧化物酶抗体定量检测在甲状腺肿大患者病因诊断上的应用

目的探讨甲状腺球蛋白抗体(TGAb)和甲状腺过氧化物酶抗体(TPOAb)定量检测在甲状腺肿大患者病因诊断上的应用。方法对291例甲状腺肿大患者血清和86例正常人血清用直接化学发光定量检测TGAb和TPOAb,并对甲状腺肿大患者检测甲功5项。结果甲状腺肿大患者TGAb和TPOAb浓度分别为(254±417)U/ml和(1001±1108)U/ml,有124例确诊为自身免疫性甲状腺炎(AITT),90例诊断为单纯性甲状腺肿大;AITT患者TGAb和TPOAb浓度和抗体检出率明显高于非AITT患者,P<0.01。结论定量检测血清TGAb和TPOAb对甲状腺肿大患者在病因诊断上有重要意义。     

Assays of TSH-receptor antibodies in 576 patients with various thyroid disorders: their incidence, significance and clinical usefulness

The incidence and the significance of TSH-receptor antibodies in Graves' disease and in various thyroid disorders have been evaluated. TSH-binding inhibiting antibodies (TBIAb) and thyroid stimulating antibodies (TSAb) were detected in a large proportion of Graves' disease patients (TBIAb in 68.8% and TSAb in 77.8%), in a small number of patients with idiopathic myxoedema or Hashimoto's thyroiditis, and were not detected in patients with endemic euthyroid goitre, differentiated thyroid carcinoma and toxic adenoma. Furthermore, TSH-receptor antibodies were present in some patients with toxic multinodular goitre (TBIAb in 12.7% and TSAb in 15.9%). When TSH-receptor and other thyroid autoantibodies were compared, it was found that 13 of the 15 Graves' patients with negative tests for thyroglobulin and thyroid microsomal antibodies were positive for TSH-receptor antibodies. On the other hand, 9 of the 11 patients with toxic multinodular goitre who had positive TSH-receptor antibody tests, also had serum thyroglobulin and/or thyroid microsomal antibodies. No significant differences in the prevalence of TSH-receptor antibodies were found in Graves' patients irrespective of the presence of ophthalmopathy or pretibial myxoedema. Elevated TBIAb activity at the end of anti-thyroid drug treatment was found in 52.9% of Graves' patients who subsequently relapsed, while in Graves' patients in remission TBIAb was always negative. TSH-receptor antibody results were not predictive of the outcome of radioiodine treatment in Graves' disease. Finally no correlation could be found between TBIAb and TSAb in Graves' disease and Hashimoto's thyroiditis. In conclusion: the high incidence of TSH-receptor antibodies in Graves' disease confirms their pathogenetic role in the development of hyperthyroidism; TSH-receptor antibodies in Graves' disease are not significantly associated with the presence of ophthalmopathy or pretibial myxoedema; TSH-receptor antibody assays may be useful for the diagnosis of Graves' disease in the absence of other signs of autoimmunity. TBIAb seems to be a good predictor of relapse in Graves' patients treated with anti-thyroid drugs; a fraction of toxic multinodular goitre could be a nodular variant of Graves' disease.     

Prognostic value of thyroid stimulating antibodies and TSH-binding inhibiting immunoglobulins in the follow-up of Graves' disease

Summary The prognostic value of the determinations of autoantibodies in Graves' disease is still questionable. So far, the role of different assay procedures used has not been intensively investigated. We simultaneously applied two different techniques, a radioreceptor assay and a T3 releasing in vitro assay, in the follow-up of patients with Graves' disease to directly compare the course of the antibody activities determined by these assays and to find out a prognostic significance of the composition of the antibody spectrum present. The initial activities of thyroid stimulating antibodies (TSAb) and TSH-binding inhibiting immunoglobulins (TBII) were not significantly correlated in patients before treatment. During a 12-month antithyroid medication antibody titres showed a concordant course in the majority of patients. In 6 of 25 patients, however, a discordant behaviour was clearly documented including dose-response curves. At the end of treatment, the patients could be divided into three groups: group I included 5 patients positive for both TSAb and TBII, group II 6 patients positive for TBII and negative for TSAb and group III 14 patients negative for both of them. During the following survey of 18 months all patients of group I, 2 patients of group II and 6 patients of group III experienced a relapse of hyperthyroidism. In conclusion, TSAb and TBII activities dissociate in some patients during antithyroid drug therapy. For the individual patient, the disappearance of both TSAb and TBII was no certain indicator for a longstanding remission of Graves' hyperthyroidism. The persistence of TSAb seems to be more reliably associated with persisting or rapidly relapsing disease than the persistence of TBII.Abbreviations cAMP Cyclic Adenosine Monophosphate - GD Graves' disease - T3 Triiodothyronine - T4 Tetraiodothyronine - TBII TSH-binding inhibiting immunoglobulins - TRH TSH releasing hormone - TSAb Thyroid stimulating antibodies - TSH Thyroid stimulating hormone     

Childhood thyroid autoimmunity and relation to islet autoantibodies in children at risk for type 1 diabetes in the diabetes prediction in skåne (DiPiS) study

Abstract

Background: The aim was to determine prevalence and age at seroconversion of thyroid autoimmunity in relation to islet autoantibodies, gender and HLA-DQ genotypes in children with increased risk for type 1 diabetes followed from birth.

Methods: In 10-year-old children (n?=?1874), blood samples were analysed for autoantibodies against thyroid peroxidase (TPOAb), thyroglobulin (TGAb), glutamic acid decarboxylase 65 (GADA), Zink transporter 8 (ZnT8R/W/QA), insulinoma-associated protein-2 (IA-2A), insulin (IAA) and HLA-DQ genotypes. Prospectively collected samples from 2 years of age were next analysed for TPOAb, and TGAb and, finally, in confirming samples at 11–16 years of age along with TSH and FT4. Frequencies were tested with Chi-square or Fischer’s exact tests, autoantibody levels with Wilcoxon and correlations between autoantibody levels with Spearman’s rank correlation test.

Results: The prevalence of thyroid autoimmunity was 6.9%, overrepresented in girls (p?<?.001) also having higher TPOAb levels at 10 years (p?=?.049). TPOAb was associated with GADA (p?=?.002), ZnT8R/W/QA (p?=?.001) and IA-2A (p?=?.001) while TGAb were associated with ZnT8R/W/QA (p?=?.021). In boys only, TPOAb were associated with GADA (p?=?.002), IA-2A (p?=?.001), ZnT8R/W/QA (p?=?.001) and IAA (p?=?.009), and TGAb with GADA (p?=?.013), IA-2A (p?=?.005) and ZnT8R/W/QA (p?=?.003). Levels of IA-2A correlated to both TPOAb (p?=?.021) and to TGAb (p?=?.011). In boys only, levels of GADA and TGAb correlated (p?=?.009 as did levels of IA-2A and TPOAb (p?=?.013). The frequency and levels of thyroid autoantibodies increased with age. At follow-up, 22.3% had abnormal thyroid function or were treated with thyroxine.

Conclusions: Thyroid autoimmunity and high TPOAb levels were more common in girls. In contrast, in boys only, there was a strong association with as well as correlation between levels of thyroid and islet autoantibodies. It is concluded that while girls may develop autoimmune thyroid disease (AITD) independent of islet autoantibodies, the risk for thyroid disease in boys may be linked to concomitant islet autoimmunity.     

Immunology of the thyrotropin receptor.

Antibodies to the thyrotropin receptor appear to be responsible for hyperthyroidism in Graves' disease. The antibodies, described as thyroid-stimulating antibodies (TSAb) mimic the effects of thyrotropin (TSH) by binding to the TSH receptor and activating adenylate cyclase. TSAb consist of an electrophoretically heterogeneous population of IgG and the thyroid-stimulating site is formed by combination of heavy and light chains in the Fab part of the molecule. Binding studies indicate that the TSAb molecule interacts monovalently with membrane bound TSH receptors and that TSAb consists of an antibody population which shows a restricted heterogeneity with regard to TSH receptor affinity. Studies in patients with Graves' disease and hyperthyroidism indicate that the levels of TSAb correlate well with thyroidal iodine uptake and the absence of pituitary control of thyroid function. However in some patients with ophthalmic Graves' disease or autoimmune thyroiditis there is evidence of serum antibodies which interact with the TSH receptor but are unable to stimulate thyroid function.     

Thyroid function tests

About 80% of thyroid disease consists of thyroid-specific autoimmune diseases, Hashimoto's disease and Grave's disease. To diagnose thyroid diseases, testings for (1) thyroid function and (2) pathogenetic autoantibodies are indispensable. To assess thyroid function, serum hormone concentrations, such as TSH, FT4 and FT3 are measured. Among these hormones, serum TSH concentrations are the most reliable and informative regarding thyroid function, correcting indicating a hyperthyroid, euthyroid or hypothyroid state. Therefore, TSH measurement appears to be the first choice in selecting the hormone determination. Reference intervals for normal healthy subjects of TSH are around 0.4-5.0 microU/ml. The second choice for thyroid function assessment are FT4 which supersedes total T4(TT4). TT4 is affected by changes in serum thyroid hormone binding proteins(TBG, TTR, Albumin). For example, euthyroid pregnant women whose serum TBG are physiologically higher than those of non-pregnant women show augmentation of TT4. However, FT4 depicts within reference intervals, although measurement of FT4 alone is unable to detect any abnormality of thyroid hormone binding proteins. According to its plasma concentration and binding affinity, FT3 measurement deserves no more significance than T3. Another important test for thyroid diseases is to detect serum autoantibodies against thyroid tissues, such as TgAb, TPOAb. Much more important is TSH receptor antibody which differentiates Graves' disease from Hashimoto's thyroiditis. In patients who show hyperthyroidism and some very uncommon hypothyroidism, TSH receptor antibodies should be measured. Three indicators are available as routine tests; TRAb measured by radioreceptor assay; TSAb determined by bioassay using cultured porcine thyroid cells. Usually, TRAb activity clinically correlates well with TSAb. TSBAb was initially discovered in patients with severe hypothyroidism with atrophic thyroid gland. TSBAb blocks thyroid stimulating activity of TSH and consequently causes severe hypothyroidism. TRAb and TSAb are very useful to diagnose and follow patients with Grave's disease.     

测定血清TGAb和TPOAb在自身免疫性甲状腺疾病中的临床价值

为探讨自身免疫性甲状腺疾病(AITD)患者血清TGAb和TPOAb浓度及临床价值,用RIA测定175例AITD组患者、64例非AITD组患者和57名对照组血清TGAb和TPOAb浓度.结果表明,AITD组中GD、HT患者血清TGAb和TPOAb浓度显著高于对照组(P<0.01),而非AITD组与对照组比较无显著性差异(P>0.05).本文认为检测TGAb和TPOAb有助于了解AITD的发病机制,对AITD的诊治及预后判断具有一定的临床价值.     

Immunological of the Thyrotropin Receptor

Antibodies to the thyrotropin receptor appear to he responsible for hyperthyroidism in Graves disease. The antibodies, described as thyroid-stimulating antibodies (TSAb) mimic the effects of thyrotropin (TSH) by binding to the TSH receptor and activating adenylate cyclase. TSAb consist of an electrophoretically heterogeneous population of IgG and the thyroid-stimulating site is formed by combination of heavy and light chains in the Fab part of the molecule. Binding studies indicate that the TSAb molecule interacts monovalently with membrane bound TSH receptors and that TSAb consists of an antibody population which shows a restricted heterogeneity with regard to TSH receptor affinity. Studies in patients with Graves disease and hyperthyroidism indicate that the levels of TSAb correlate well with thyroidal iodine uptake and the absence of pituitary control of thyroid function. However in some patients with ophthalmic Graves' disease or autoimmune thyroiditis there is evidence of serum antibodies which interact with the TSH receptor but are unable to stimulate thyroid function.